Middle East Fertility Society Journal Vol. 11, No. 1, 2006 Copyright Middle East Fertility Society Intrauterine insemination: pregnancy rate and its associated factors in a university hospital in Iran Zahra Rezaie, M.D. Ozra Azmodeh, M.D. Neda Heydari Hamadani, M.D. Mirza Koochak Khan Hospital, Tehran University of Medical Sciences, Tehran, Iran. ABSTRACT Objective: To determine pregnancy rate and its associated factors in Intrauterine Insemination (IUI) in a University ART center in Tehran, Iran. Materials and Methods: A retrospective descriptive study was conducted on all available records of infertile patients (200 cases) who had undergone IUI treatment for their infertility problems in Mirza Koochak Khan ART center, between 1999 and 2000. The necessary data were collected and then analyzed with Chi-square test with a significant level of 0.05. Results: 200 infertile couples did 575 IUI cycles. Pregnancy rate was 19.5% per couple and 6.8% per cycle (39 cases). The pregnancy rate in couples with secondary infertility was significantly higher than those with primary infertility (47.4% vs. 8.4%, P<0.0001) and patients with more than 60% normal sperm morphology (NSM) had higher pregnancy rate than those with less than 60% NSM (24.3% vs. 7.7%, P=0.0052). Pregnancy rate tended to increase when the number of large follicles increased at the time of IUI (From 6.7% in 1-2 oocytes to 15.7% in >5 oocytes, P=0.0095). As the numbers of IUI treatment cycles increased, the success rate per cycle decreased. There was a significant difference in pregnancy rate according to kind of drug used for ovarian stimulation. Pregnancy rate was 11.5% with HMG, compared to 7.2% with clomiphene citrate and HMG (P=0.052). Pregnancy rate with twice IUI per cycle was significantly higher than those who had one IUI per cycle (24.1% versus 11.8%, P<0.05). The highest pregnancy rate was seen in 21-30 years old patients (46.5%) and the lowest in women with more than 36 years of age, while no pregnancy occurred in patients less than 20 years of age. The frequency of twin pregnancy and low birth weight infants was 25.6% (10 subjects) and 14.3% (7 subjects) respectively. Conclusion: It seems that IUI provides better results in patients with secondary infertility, with >60% NSM and with >5 large follicles at the time of treatment. Pregnancy rate does not increase with increasing the number of treatment cycles and ovarian stimulation with HMG is associated with relatively higher pregnancy rate. Key words: IUI, pregnancy rate, infertility, ovarian stimulation. Intrauterine insemination is a common procedure used for the treatment of infertility. If it is performed based on appropriate indications and accurate protocol, it will be a convenient method (1, 2). IUI is easier, safer and inexpensive in comparison with other ART methods. The outcome of IUI is associated with some factors. Corresponding author: Zahra Rezaie: Department of Infertility, Mirza Koochak Khan Hospital, North Ostad Nejatollahi, Karim Khan Zand Blvd, Tehran 15978, Iran. Phone/Fax: #98-21-890 4172 Email: rezaizah@sina.tums.ac.ir Pregnancy rate per cycle of IUI ranges from 2.7% to 11.4 % (1,2). In some studies on IUI procedures, maternal age, number of IUI and cause of infertility were related to the success rate of pregnancy (3). Edward et al. reviewed 18 studies which used IUI and concluded that couples with less than 3 years duration of infertility, had highest chance to conceive (4). Plosker et al. performed 381 IUI cycles for 215 infertile couples, and reported that the pregnancy Vol. 11, No. 1, 2006 Rezaie et al. Factors determining pregnancy rate in IUI 59
Table 1. Demographic and clinical specifications of infertile couples undergoing IUI in M.K.K. Hospital 1999-2000. Number (%) Age (years) 18-20 2 (1.0) 21-25 56 (28.0) 26-30 66 (33.0) 31-35 44 (22.0) 36-40 32 (16.0) Duration of infertility (years) <2 66 (33.0) 2-5 80 (40.0) 6-10 44 (22.0) >10 10 (5.0) Type of infertility Primary 143 (71.5) Secondary 57 (28.5) Cause of infertility Male 95 (47.5) Uterine tube 36 (18.0) Ovarian 29 (14.5) Cervical 6 (3.0) Uterine 6 (3.0) Endometriosis 6 (3.0) Idiopathic 22 (11.0) rate decreased when the maternal age or the number of treatment cycles increased (5). Evaluation of 610 IUI cycles on 174 infertile couples through the years of 1990-91, showed that the pregnancy rate is higher in younger women. Shorter infertility period, secondary and unexplained infertility have a higher rate of success. The number of motile sperms and number of IUI per cycle are other factors associated with success rate of treatment (6). Wang B et al. analyzed 186 patients and 216 cycles of IUI, and reported that IUI is of more applied value for male and cervical factor infertility. With these factors in mind, choosing the most suitable insemination time is the key to increasing pregnancy rate (7). Pregnancy rate was 12.8% per cycle for IUI in Mirza Koochak Khan Hospital in the year 1996. Women 21-25 years old had highest pregnancy rate. (8) This study was conducted on 200 infertile couples who had undergone IUI procedure in Mirza Koochak Khan Hospital during 1999-2000, to estimate the pregnancy rate in IUI and to determine the related factors for it. MATERIALS AND METHODS This retrospective descriptive study was performed on all infertile couples who had undergone IUI in the ART center of Mirza Koochak Khan Hospital during the years 1999-2000. The medical records including, duration of infertility (years), type of infertility (primary, secondary), cause of infertility (male, female, idiopathic) number of sperms, motility, morphology of sperms, number of IUI per cycle, number of follicles, the type of induction of ovulation and the number of IUI cycles of these couples were reviewed then pregnancy rate and its associated factors were compared. The couples were considered eligible for this study if the necessary information were obtained from their medical records. The uncertain or uncompleted medical records were excluded form this study. Missing data from the medical records were completed by asking the subjects by calling their phone, if it was necessary. Every effort was made to maximize privacy of records. Statistical analysis was performed using SPSS software (version 10). The comparisons were performed using Chi-square test (a=0.05). RESULTS Two hundred infertile couples underwent 575 cycle of IUI. Women's ages ranged from 18 to 40 years with a median age of 27 years. The majority of subjects (73%) experienced maximum 5 years duration of infertility. 71.5% had primary infertility and male factor was the most frequent cause of infertility (95 cases, 47.5%) (Table 1). The pregnancy rates were 19.7% (39 cases) and 6.8% per patient and per cycle respectively. The highest pregnancy rate occurred in 21-25 years old women (26.8%) and the lowest occurred in women more than 36 years old (9.4%). There was no pregnancy in women less than 20 years old. The association between age and success rate was not statistically significant (p=0.081) (Table 2). Difference of pregnancy rate between primary (8.4%) and secondary infertility (47.4%) was significant (p<0.0001) (Table 2). The pregnancy rate decreased as the duration of infertility increased 60 Rezaie et al. Factors determining pregnancy rate in IUI MEFSJ
Table 2. Comparison of results of treatment by studying factors in infertile couples undergoing IUI in M.K.K. Hospital 1999-2000. Infertility Pregnancy Signification Age (years) n (%) n (%) 18-20 2 (100.0) 0 (0.0) N.S. 21-25 41 (73.2) 15 (26.8) N.S. 26-30 53 (80.3) 13 (19.7) N.S. 31-35 36 (81.8) 8 (18.2) N.S. 36-40 29 (90.6) 3 (9.4) N.S. Duration of infertility (years) <2 50 (75.8) 16 (24.2) N.S. 2-5 64 (80.0) 16 (20.0) N.S. 6-10 37 (84.1) 7 (15.9) N.S. >10 10 (100.0) 0 (0.0) N.S. Type of infertility Primary 131 (91.6) 12 (8.4) P>0/0001 Secondary 30 (52.6) 27 (47.4) P>0/0001 Cause of infertility Male 79 (83.2) 16 (16.8) N.S Female 64 (77.1) 19 (22.9) N.S Idiopathic 18 (81.8) 4 (18.2) N.S Number of sperms <10 106 7 (87.5) 1 (12.5) N.S (10-20) 106 22 (78.6) 6 (21.4) N.S >20 106 132 (80.5) 32 (19.5) N.S Normal motility sperm %60 147 (79.9) 37 (20.1) N.S >%60 14 (87.5) 2 (12.5) N.S Normal morphology sperm %60 109 (75.7) 35 (24.3) P=0.0052 >%60 52 (92.3) 4 (7.7) P=0.0052 Number of IUI/cycle One 67 (88.2) 9 (11.8) P<0.05 Two 94 (75.9) 30 (24.1) P<0.05 (From 24.2% for less than 2 years duration to 0.0% for more than 10 years duration of infertility) (p=0.076) (Table 2). The relationship between pregnancy rate and the cause of infertility was not statistically significant (p=0.076) (Table 2). The highest rate of pregnancy occurred in subjects with uterine factor infertility (33.3%) and the lowest (16.7%) occurred in patients with cervical and endometriosis factor. Pregnancy rate did not have any relation to sperm count and motility, but it was related to sperm morphology. When sperm morphology was more than 60% normal, pregnancy rate was 24.3% comparing to 7.7% when it was less than 60% normal (p=0.005) (Table 2). There was not any association between pregnancy rate and the number of large follicles (Table 3). Pregnancy rate was significantly higher when HMG was used for ovulation induction (11.5%), compared to 7.2% with "clomiphene citrate + HMG" or to using "clomiphene citrate" as the sole medicine for ovulation induction (P=0.025) (Table 3). Pregnancy rate was significantly higher with increasing the number of IUI per cycles, being 24.1% and 11.8% in two IUI per cycles and one IUI per cycle respectively (Table 2). The highest rate of successful pregnancy was achieved in the first therapeutic cycle (20 out of 200 cases, 10%), there was just one pregnancy (out of 57 cases, 1.8%) in the fourth cycle and no pregnancies occurred in the fifth and sixth repeated cycles (p<0.05) (Table 3). In this study 10 twin pregnancies (25.6%) occurred, and 42 (85.7%) of 49 newborns were low birth weight. No fetal congenital malformations occurred in any case. Vol. 11, No. 1, 2006 Rezaie et al. Factors determining pregnancy rate in IUI 61
Table 3. Comparison of results of treatment by studying factors in infertile couples (whom have undergone) IUI in M.K.K. Hospital 1999-2000. Not pregnant n=536 Pregnant n=39 signification Number of follicles n (%) n (%) 1-2 144 (96.0) 6 (4.0) N.S 3-5 231 (93.5) 16 (6.5) N.S >5 161 (90.5) 17 (9.5) N.S Induction ovulation Clomiphene citrate 210 (96.3) 8 (3.7) P<0.025 HMG 108 (88.5) 14 (11.5) P<0.025 HMG+ clomiphene citrate 218 (92.8) 17 (7.2) P<0.025 Cycles First 180 (90.0) 20 (10.0) P<0.05 Second 159 (92.4) 13 (7.6) P<0.05 Third 110 (95.7) 5 (4.3) P<0.05 Fourth 56 (98.2) 1 (1.8) P<0.05 Fifth 23 (100.0) 0 (0.0) P<0.05 Sixth 8 (100.0) 0 (0.0) P<0.05 DISCUSSION Findings of this study were comparable to most other studies in this field. Pregnancy rate per couple was 19.7% and it was 6.8% per cycle in this study, comparing to anther study being 22.6% and 8% rates respectively (6). In another Mirza Koochak Khan Hospital study, pregnancy rate was 21.6% per couple and 12.8% per cycle (8). In this study the rate of pregnancy decreased with increasing age, which is comparable to a previous study in our hospital (8) and also to other studies (2, 5, 6). Paulmyer LO, et al. concluded in their study that the pregnancy rate decreased with increasing infertility duration (2), which was the same conclusion as our study, and the study of Iberico G et al (9). Highest success rates occurred with infertility due to uterine factor, tubal and ovarian factors respectively. These finding were comparable to other studies such as Plosker SM study. The highest pregnancy rate occurred in women with ovarian factor in one study (5) and in female factor in a previous study in Mirza Koochak Khan Hospital (8). In our study the pregnancy rate was more in secondary infertility and this agrees with the results of Edward E, et al. (4). Zhao Y et al. concluded that a forward open progression score of 3 to 4 in a processed specimen is necessary for IUI success (10). The relation between pregnancy rate and the number or motility of sperm was not confirmed in our study, which is not similar to others who reported a relation between pregnancy rate and number or motility of sperm (2, 6 and 11). In our study, the success rate was related to sperm morphology. Wainer R et al. in a retrospective study of 889 couples who did 2564 IUI cycles between Jan. 1991 and Dec. 2000 reported that sperm morphology, assessed before or after preparation, was not in itself a significant factor that affected the likelihood of IUI success (12). We had 9.5% success rate per cycle with more than five mature follicles comparing to 4% with 1 to 2 mature follicles, which was statistically nonsignificant. However Iberico concluded that the best results would be obtained with 2 or 3 induced follicles (9). Plosker SM, et al. stated that existence of at least two mature follicles is necessary for IUI therapy (5). We got better results with HMG usage for ovulation induction, than with clomiphene citrate + HMG. The least pregnancy rate was obtained when clomiphene citrate only was used for ovulation induction. 62 Rezaie et al. Factors determining pregnancy rate in IUI MEFSJ
Plosker SM, et al. also reported that using HMG is associated with better results (5) and Osia SH, showed highest pregnancy rate with HMG + HCG (8). The pregnancy rate was higher when 2 times IUI per cycle was performed, and the highest rate was obtained in the first IUI treatment cycle. These findings confirm previous results (2, 5,6). 25.6% of our pregnancies were twin, and no cases of fetal malformation occurred. This is satisfactory comparing it to Isaksson R, et al. study. They observed 25% of multiple pregnancy in their study and reported 18.2% of partial or complete fetal malformation (13). Finally we conclude that IUI is a convenient procedure for appropriate indications. We can obtain better results from this procedure with cases of secondary infertility, normal sperm morphology?60% and with the use of HMG as ovulation induction agent. Also performing twice IUI per cycle increases the rate of success. REFERENCES 1. Speroff L, Glass RH, Kase NG. Clinical Gynecologic Endocrinology and Infertility, Fifth Edit; 1994: 760-806. 2. Paulmyer-Lacroix O, Molle L, Nozet A. et al. Intrauterine insemination with the husband's sperm: conclusions of five years experience. Contracept Fertil Sex. 1998 Apr; 26(4): 300-6. 3. Intrauterine insemination IUI: the effect of ovarian stimulation and infertility diagnosis on pregnancy outcome. Clin Exp Obstet Gynecol. 1998; 25(4): 144-6. 4) Edward Edi, Wallach EE, Kempers RD. Modern Trends in Infertility and conception control Volume 4. 1988. 487-498. 4. Plosker SM, Jacobson W, Amato P. Predicting and optimizing success in an intra-uterine insemination programme. Hum Reprod. 1994 Nov; 9(11): 2014-21. 5. Rojanasakul A, Suchartwatnachai C, Choktanasiri W, Wongkularb A, Hansinlawat P, Chinsomboon S. Two years' experience of intrauterine insemination for the treatment of infertility. J Med Assoc Thai. 1993 Aug; 76(8): 415-23. 6. Wang B, Hu Y, Sun H, Zhang N, Xu Z. Investigation of correlative factors affecting successful intrauterine insemination. Zhonghua Nan Ke Xue. 2004 Jul; 10(7): 526-9. 7. Osia SH. (Thesis, 1996) Evaluation of 153 patients, which treated, by 258 IUI cycles in Mirza Koochak Khan Hospital. Tehran Medicine College Library. 8. Iberico G, Vioque J, Ariza N, Lozano JM, Roca M, et al. Analysis of factors influencing pregnancy rates in homologous intrauterine insemination. Fetil Steril. 2004 May; 81(5): 1308-13. 9. Zhao Y, Vlahos N, Wyncott D, Petrella C, Garcia J, et al. Impact of semen characteristics on the success of intrauterine insemination. J Assist Reprod Genet. 2004 May; 21(5): 143-8. 10. Yalti S, Gurbuz B, Sezer H, Celik S. Effects of semen characteristics on IUI combined with mild ovarian stimulation. Arch Androl. 2004 Jul-Aug; 50(4): 239-46. 11. Wainer R, Albert M, Dorion A, Bailly M, Bergere M, et al. Influence of the number of motile spermatozoa inseminated and of their morphology on the success of intrauterine insemination. Hum Reprod. 2004 Sep; 19(9): 2060-5. 12. Isaksson R, Tiitinen A. Obstetric outcome in patients with unexplained infertility: comparison of treatmentrelated and spontaneous pregnancies. Acta Obstet Gynecol Scand. 1998 Sep; 77(8): 849-53. Received on July 2, 2005; revised and accepted on August 16, 2005 Vol. 11, No. 1, 2006 Rezaie et al. Factors determining pregnancy rate in IUI 63